The present invention relates to pressure determination, in particular in a high performance liquid chromatography application.
Many technical fields require pressure measurement, e.g. as disclosed in U.S. Pat. Nos. 3,985,021, 5,645,684, DE 19832681, U.S. Pat. No. 7,252,006, WO 2007/014336, U.S. Pat. No. 7,509,869, WO 2011/013111, M. J. Kohl, S. I. Abdel-Khalik, S. M. Jeter, D. L. Sadowski, “A microfluidic experimental platform with internal pressure measurements”, Sensors and Actuators A 118 (2005), pages, 212 to 221, or US 2009/238722
In high performance liquid chromatography (HPLC), a liquid has to be provided usually at a very controlled flow rate (e. g. in the range of microliters to milliliters per minute) and at high pressure (typically 20-100 MPa, 200-1000 bar, and beyond up to currently 200 MPa, 2000 bar) at which compressibility of the liquid becomes noticeable. For liquid separation in an HPLC system, a mobile phase comprising a sample fluid (e.g. a chemical or biological mixture) with compounds to be separated is driven through a stationary phase (such as a chromatographic column packing), thus separating different compounds of the sample fluid which may then be identified. The term compound, as used herein, shall cover compounds which might comprise one or more different components.
The mobile phase, for example a solvent, is pumped under high pressure typically through a chromatographic column containing packing medium (also referred to as packing material or stationary phase). As the sample is carried through the column by the liquid flow, the different compounds, each one having a different affinity to the packing medium, move through the column at different speeds. Those compounds having greater affinity for the stationary phase move more slowly through the column than those having less affinity, and this speed differential results in the compounds being separated from one another as they pass through the column. The stationary phase is subject to a mechanical force generated in particular by a hydraulic pump that pumps the mobile phase usually from an upstream connection of the column to a downstream connection of the column. As a result of flow, depending on the physical properties of the stationary phase and the mobile phase, a relatively high pressure drop is generated across the column.
The mobile phase with the separated compounds exits the column and passes through a detector, which registers and/or identifies the molecules, for example by spectrophotometric absorbance measurements. A two-dimensional plot of the detector measurements against elution time or volume, known as a chromatogram, may be made, and from the chromatogram the compounds may be identified. For each compound, the chromatogram displays a separate curve feature also designated as a “peak”. Efficient separation of the compounds by the column is advantageous because it provides for measurements yielding well defined peaks having sharp maxima inflection points and narrow base widths, allowing excellent resolution and reliable identification and quantitation of the mixture constituents. Broad peaks, caused by poor column performance, so called “Internal Band Broadening” or poor system performance, so called “External Band Broadening” are undesirable as they may allow minor components of the mixture to be masked by major components and go unidentified.
Also in liquid chromatography, pressure measurement of a fluid may be desired e.g. by applying pressure detectors. While pressure detection might be beneficial at virtually any position within the flow path, only a limited number of pressure detectors are typically applied at a few positions only within the flow path, in particular not to add additional dead volumes but also for reasons of additional costs as well as limited accuracy and applicable pressure range of most available pressure detectors.
WO 2011/143268 A1 discloses a pressure sensing and flow control in diffusion-bonded planar devices for fluid chromatography.
WO 2013/037414 A1, by the same applicant, discloses a fluidic chip device for processing a fluid. The fluidic chip device comprises a plurality of layers laminated to one another. At least a part of the layers comprises a patterned section of an alternating sequence of bars and fluidic channels for conducting the fluid under pressure. The patterned section is configured for being displaceable in response to the pressure. A pressure detector responds to the displacement of the patterned section by generating a detector signal being indicative of a value of the pressure.